Term
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Definition
mediates the initial protection against infections
"natural" or "native" immunity
always present in healthy individuals
prepared to block entry of microbes and rapidly eliminate microbes that do succeed in entering host tissues |
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Term
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Definition
develops more slowly and mediates later (than innate)
"specific" or "acquired" immunity
stimulated by microbes that invade tissues
adaptive to the presence of microbial invaders |
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Term
| What are the mechanisms of innate immunity? |
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Definition
epithelial barriers, phagocytes, dendritic cells, complement, NK cells
Occurs from 0-12 hrs post infection (P.I.) |
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Term
| What are the mechanisms of adaptive immunity? |
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Definition
B lymphocytes, antibodies
T lymphocytes, effector T cells
occurs 1-6 days PI |
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Term
| What is the function of humoral immunity? |
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Definition
Blocks infections and eliminates extracellular microbes
B lymphocytes recognize extracellular microbes and secrete antibodies
B cells are able to recognize many different types of molecules including proteins carbohydrates and lipids |
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Term
| What is the function of cell-mediated immunity? |
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Definition
1. Activation of macrophages to kill phagocytosed microbes by helper T cells
2. kill infected cell and eliminate reservoirs of infection by cytotoxic T cells |
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Term
| What are the different types of lymphocytes and their functions? |
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Definition
1.B lymphocytes: mediators of humoral immunity, produce antibodies
2.CD4+ Helper Tcells: help B cells produce antibodies and help phagocytes destroy ingested microbes
3.CD4+ Regulatory: prevent or limit immune responses
4.CD8+: cytotoxic kill cells harboring intracellular microbes
5.NK cells: kill infected host cells but do not express clonally distributed antigen receptors, components of innate immunity capable of rapidly attacking infected cells, Kill virus infected cells and produce the macrophage-activating cytokine IFN-g |
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Term
| What are three types of APCs and their functions? |
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Definition
Dendritic cells: initiation of T cell responses
macrophages: initiation and effector phase of cell-mediated immunity
Follicular dendritic cells: display of antigens to B lymphocytes in humoral immune responses, do NOT present antigens to T cells |
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Term
| What are the peripheral lymphoid organs? |
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Definition
lymph nodes, spleen, mucosal and cutaneous immune systems
organized to optimize interactions of antigens, APCs, and lymphocytes in a way that promotes the development of adaptive immune responses |
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Term
| How are B cells segregated into different anatomic compartments within peripheral lymphoid organs? |
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Definition
| B cells are located in the follicles because FDCs secrete a chemokine for which naive B cells express a receptor. Chemokine is secreted all the time and it attracts B cells from the blood into the follicles of lymphoid organs |
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Term
| How are T cells segregated into different anatomic compartments within peripheral lymphoid organs? |
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Definition
| T cells are segregated in the paracortex of lymph nodes and the periarteriolar lympohid sheaths of the spleen because naive T cells express a receptor called CCR7 that recognizes chemokines that are produced in these regions of the lymph nodes and spleen |
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Term
| How do niave T cells enter lymph nodes? |
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Definition
| Through specialized postcapillary venules called high endothelial venules that are present in the lymph nodes. Naive T cells express a surface receptor called L-selectin that binds to carbohydrate ligands that are expressed only on the endothelial cells of HEVs (spleen does not contain HEVs) |
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Term
| How are activated T cells drawn out of the lymph nodes into the circulation? |
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Definition
| T cells are activated to proliferate and differentiate. During this process, the cells reduce expression of adhesion molecules and chemokine receptors that keep naive cells in the lymph nodes. T cells also increase their expression of receptors for a phospholipid called sphingosine-1-phosphate, which has a higher concentration in the blood than in lymph nodes so activated cells are drawn out |
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Term
| What are the three main strategies of the adaptive immune response? |
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Definition
1. secreted antibodies bind to extracellular microbes, block their ability to infect host cells, and promote their ingestion and subsequent destruction by phagocytes
2. phagocytes ingest microbes and kill them, and helper T cells enhance the microbicidal abilities of the phagocytes
3. cytotoxic t cells destroy cells infected by microbes that are inaccessible to antibodies |
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Term
| what is heavy chain class (isotype) switching? |
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Definition
| Production of different antibodies all with the same specificity. Provides plasticity in the antibody response, enabling antibodies to serve many functions |
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Term
| What class of antigen stimulates secretion of mainly IgM? |
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Definition
| Polysaccharides and lipids |
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Term
| What class of antigen stimulates helper T cells and what do they induce? |
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Definition
| Protein antigens stimulate helper T cells, which induce the production of antibodies of IgG, IgA, and IgE |
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Term
| What does the term homeostasis mean with regards to the immune response? |
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Definition
| A majority of effector lymphocytes induced by an infectious pathogen die by apoptosis after the microbe is eliminated, thus returning the immune system to its basal resting state. As stimuli from microbes is eliminated, the activated lymphocytes are no longer kept alive. |
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Term
| What structures does the innate immune system recognize? |
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Definition
1. structures shared by various classes of microbes that are not present on host cells such as LPS or endotoxin, terminal mannose residues, double-stranded RNA
pathogen-associated molecular patterns
2. structures of microbes that are often essential for the survival and infectivity of the microbe
3. molecules that are released from stressed or necrotic cells called damage-associated molecular patterns |
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Term
| What are 2 of the most important trc factors activated by TLR signals? |
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Definition
1.NFkB- promotes expression of various cytokines and endothelial adhesion molecules
2. IRF-3- interferon response factor 3, stimulates production of type I interferons, cytokines that block viral replication |
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Term
| What are the locations of receptors in the innate immune system? |
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Definition
| TLRs for example can be located on the cell surface, endosomes (they may be resident in the ER and may be rapidly translocated to endosomes in response to microbe entry) and cytoplasm for viral RNA or bacterial peptides |
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Term
| Where are TLR-1,-2,-6 located and what do they recognize? |
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Definition
They are located on the plasma membrane/cell surface
Recognize bacterial peptidoglycan, lipoprotein, lipotechoic acid, and others |
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Term
| Where are TLR-4 receptors found and what do they recognize? |
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Definition
Found on cell surface/plasma membrane
Recognize gram-negative bacterial LPS, fungal mannans, viral envelope proteins |
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Term
| Where are TLR-5 receptors found and what do they recognize? |
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Definition
Found on cell surface/plasma membrane
Recognize bacterial flagellin |
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Term
| Where are TLR-3,-7,-8,-9 receptors located and what do the recognize? |
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Definition
Found on endosomal membrane
Recognize microbial nucleic acids (single-stranded RNA, unmethylated CpG dinucleotides) |
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Term
| What signaling mechanisms do TLRs activate? |
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Definition
Recruitment of adapter proteins
Recruitment and activation of protein kinases
Activation of transcription factors (NFkb and IRF-3)
Gene transcription
Expression of : inflammatory cytokines (TNF, IL-1, IL-12), Chemokines (IL-8, MCP-1, RANTES), endothelial adhesion molecules (E-selectin), costimulatory molecules (CD80, CD86) Antiviral cytokines (IFN-a/b) |
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Term
| What are the three major interfaces between the body and the external environment? |
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Definition
the skin, the GI tract, and the respiratory tract
All three portals of entry are lined by continuous epithelia that physically interfere with the entry of microbes |
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Term
| What are intraepithelial lymphocytes? |
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Definition
| type of lymphocyte that belongs to the T cell lineage but expresses antigen receptors of limited diversity. Some are composed of gamma/delta chains that are similar but not identical to the highly diverse alpha beta t cell receptors. Often recognize microbial lipids and other structures that are shared by microbes of the same type. Serve as sentinels against infectious agents that attempt to breach the epithelia. |
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Term
| What are the 3 main functions of epithelia in innate immunity? |
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Definition
1. physical barrier to infection
2. killing of microbes by locally produced antibiotics
3. killing of microbes and infected cells by intraepithelial lymphocytes |
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Term
| What are the stages in maturation of mononuclear phagocytes? |
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Definition
1. Bone marrow stem cell
2. blood monocyte
3. tissue macrophage
4. differentiation - microglial cells (CNS), Kupffer cells (liver), alveolar macrophages (lungs), osteoclasts (bone)
5. activation |
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Term
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Definition
| accumulation of leukocytes at sites of infection, with concomitant vascular dilation and increased leakage of fluid and proteins in the tissue |
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Term
| What are some of the microbicidal substances that are produced in phagolysosomes that act on ingested microbes but do not damage the phagocytes? |
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Definition
1. Phagocyte oxidase: converts molecular oxygen into superoxide anion and free radicals called ROS, which are toxic to ingested microbes
2. inducible nitric oxide synthase, catalyzes the conversion of arginine to NO
3. lysosomal proteases which break down microbial protiens |
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Term
| What is chronic granulomatous disease? |
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Definition
| Inherited deficiency of the phagocyte oxidase enzyme. Phagocytes are unable to eradicate intracellular microbes and the host tries to contain the infection by calling in more macrophages and lymphocytes resulting in collections of cells around the microbes that are called granulomas |
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Term
| What are some functions of macrophages? |
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Definition
1. produce cytokines that recruit and activate leukocytes
2. secrete growth factors and enzymes that function to repair injured tissue and replace it with CT
3. stimulate T lymphocytes and enhance adaptive immunity
4. respond to products of T cells and function as effector cells of cell-mediated immunity |
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Term
| What are the functions of NK cells? |
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Definition
1. kill host cells infected by intracellular microbes thus eliminating reservoirs of infection
2. Respond to IL-12 produced by macrophages and secrete IFN-g which activates the macrophages to kill phagocytosed microbes |
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Term
| How does the specificity of innate immunity differ from that of adaptive immunity? |
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Definition
Innate: respond to microbes, are specific for structures present on various classes of microbes, mediated by receptors encoded in the germline, not enhanced by repeat exposrue
Adaptive: directed against microbial as well as nonmicrobial antigens, specificity is much more diverse, capable of recognizing many more chemically distinct structures |
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Term
| What are examples of microbial substances recognized by the innate immune system? |
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Definition
Pathogen-associated molecular patterns: bacterial lipopolysaccharide (LPS), endotoxin, terminal mannose residues, double-stranded RNA, unmethylated CpG oligonucleotides
Damage-associated molecular patterns: molecules that are released from stressed or necrotic cells |
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Term
| What are the receptors for microbial substances? |
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Definition
Encoded in the germline and are not produced by somatic recombination of genes
pattern recognition receptors: Toll-like receptor, N-formyl methionyl receptor, mannose receptor |
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Term
| What are the mechanisms by which the epithelium of the skin prevents the entry of microbes? |
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Definition
1. Physical barrier to infection
2. killing of microbes by locally produced antibodies
3. killing of microbes and infected cells by intraepithelial lymphocytes |
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Term
| How do phagocytes ingest and kill microbes? |
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Definition
| Macrophages and neutrophils express many surface receptors that may bind microbes. First microbe binds to receptor, then phagocyte membrane zips up around microbe and it is ingested in a phagosome. Next fusion of the phagosome with lysosome occurs. Killing of the microbe happens by lysosomal enzymes in the phagolysosome (ROS and NO0 |
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Term
| What is the role of MHC molecules in the recognition of infected cells by NK cells? |
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Definition
Some viruses inhibit class I MHC expression thus when NK cell attaches to the activating ligand there is no inhibitory MHC I receptor and the NK cell is activated. This results in killing of the infected cell.
If however, the NK inhibitory receptor is engaged by self class I MHC-self peptide complex then the NK cell will not be activated. This occurs on healthy host cells. |
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Term
| What is the role of TNF ? |
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Definition
Endothelial cell activation (inflammation, coagulation)
Neutrophil activation
Fever
Synthesis of acute phase proteins in the liver
Catabolism (cachexia) in the muscle and fat
Apoptosis in many types of cells |
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Term
| What is the role of IL-12? |
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Definition
Secreted by dendritic cells and macrophages
Stimulates increased production of IFN-g in NK and T cells
Th1 differentiation |
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Term
| What is the role of type I interferon? |
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Definition
IFN-a from dendritic cells, macrophages
IFN-b fibroblasts
Stimulates anti-viral state, increased class I MHC expression and activates NK cells |
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Term
| How do innate immune responses enhance adaptive immunity? |
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Definition
| They provide second signals for activation of B and T lymphocytes. The requirement for microbe-dependent second signals ensures that lymphocytes respond to infectious agents and not to harmless, noninfectious substances |
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Term
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Definition
Different clones of T cells can see peptides only when these peptides are displayed by that individual/s MHC molecules.
TCR recognizes some residues of peptide antigen and also recognizes residues of the MHC molecule that is displaying that peptide |
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Term
| How are microbial antigens captured and displayed for T cells? |
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Definition
| Captured by APCs resident in epithelium, or they enter lymphatic vessels or blood vessels. Microbes and their antigens are transported to peripheral lymphid organs, the lymph nodes, and the spleen, where protein antigens are displayed for recognition by T cells |
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Term
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Definition
a surface receptor that is specific for chemoattracting cytokines produced in the T cell zones of lymph nodes
Activated dendritic cells lose their adhesiveness for epithelia and begin to express CCR7 and thus begin to migrate to lymph nodes
Naive T cells also express CCR7 which promotes their entry into lymph nodes |
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Term
| What is cross-presentation? |
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Definition
Dendritic cells ingest infected cells and display the antigens present in the infected cells for recognition by CD8 T cells.
Indicates that one cell type can present the antigens of other cells and prime naive T cells specific for these antigens |
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Term
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Definition
Human leukocyte antigens
They are human MHC proteins. Discovered as antigens of leukocytes that could be identified with specific antibodies |
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Term
| What is the structure of class I MHC? |
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Definition
alpha chain noncovalently attached to a protein called beta2-microglobulin that is encoded by a gene outside the MHC
alpha 1 and 2 are polymorphic
alpha 3 is invariant and contains the binding site for the T cell co-receptor CD8 |
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Term
| What is the structure of MHC class II |
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Definition
consists of 2 chains called alpha and beta
amino terminal regions of both alpha1 and beta1 contain polymorphic residues
CD4 cells can only respond to peptides presented by class II MHC molecules |
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Term
| What does it "codominantly expressed" mean |
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Definition
alleles inherited from both parents are expressed equally
all heterozygous individuals have two HLA haplotypes, one from each chromosome
This increases the number of different MHC molecules that can present peptides to T cells |
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Term
| How are antigens processed for MHC class II molecules? |
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Definition
| Microbes bind to surface receptors and are internalized. Microbial proteins enter acidic intracellular vesicles and form phgolysosomes. MHC II is synthesized in the ER but CLIP occupies the peptide binding site until it is transported to the cell surface in an exocytic vesicle. Upon fusion with the endosome containing microbial protiens, DM cleaves CLIP and a microbial peptide binds to MCH II complex |
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Term
| How are antigens processed for MHC I? |
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Definition
| Production of proteins in the cytosol which are then ubiquitinated, unfolded and broken down in a proteasome. Peptides are transported across the ER membrane by TAP and picked up by MHC I. Once the MHC I-peptide complex is form it is stablized and presented to the cell surface |
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Term
| Why is the segregation of class I and class II MHC significant? |
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Definition
| It ensures the correct, specialized immune response against microbes in different locations. Intracellular (viral) CD8, Extracellular CD4 and humoral response |
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Term
| What is an antibody composed of? |
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Definition
4 polypeptide chains, including 2 identical heavy chains and 2 identical light chains with each chain containing one variable region and one constant region
Each variable region of the heavy or light chain contains three hypervariable regions or CDRs |
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Term
| What does the hinge region of the antibody allow? |
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Definition
| Allows 2 antigen-binding Fab regions of each antibody molecule to move independently of each other, enabling them to simultaneously bind antigen epitopes that are separated from one another by varying distances |
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Term
| What is the TCR composed of? |
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Definition
membrane-bound heterodimer composed of an alpha chain and a beta chain, each chain containing one variable region and one constant region
Both TCR chains are anchored in the plasma membrane and they are not produced in a secreted form, nor do they undergo class switching or affinity maturation |
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Term
| What is the TCR composed of? |
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Definition
membrane-bound heterodimer composed of an alpha chain and a beta chain, each chain containing one variable region and one constant region
Both TCR chains are anchored in the plasma membrane and they are not produced in a secreted form, nor do they undergo class switching or affinity maturation |
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Term
| What is positive selection? |
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Definition
If the TCR of a T cell recognizes an MHC molecule in the thymus it is selected to survive. This recognition is necessary for antigen presentation later.
Selection is based on the expression of intact antigen receptor components and what they recognize. |
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Term
| What is negative selection? |
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Definition
| Eliminates potentially dangerous lymphocytes that may be capable of reacting against self antigens that are present throughout the body. |
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